We did IVF but had heaps of empty follicles – help!

Some of us do IVF, go for those scans and see hardly any follicles after all those injections. Others are relieved to see a healthy crop developing as they go through their cycles. Unfortunately, the number of follicles (or “follies”) doesn’t necessarily equate to the number of eggs collected. And for some women, a huge proportion of the follies are ’empty’. This is sooo frustrating after seeing all those follies on the screen and usually having a fantastic E2 (estrogen level) to match.

There is such a thing as “empty follicle syndrome”, but unfortunately it’s still not all that well understood, and there are various theories …

The most common explanation given by the specialists is that egg maturity and quality are related to how easy they are to get out. Those that are flushed out are lower quality than those that came out easily. ‘Empty’ follicles may not actually be empty; they may just contain very poor quality eggs. OK, there’s obviously a heavy element of truth to this (i.e. it’s a known fact about eggs in general), but the big question, of course, is whether (and how much) it applies in YOUR case. It probably does, to some extent, in just about all cases of empty follicle syndrome. But that’s actually a “There’s nothing we can do about it” diagnosis, and not much use unless you are looking forÂ a reason to switch to donor eggs or give up altogether. So, the following are some other plausible theories that may or may not apply, but many of which CAN be addressed.

One theory is that you got a dud trigger shot. It’s rare, but it can happen. And it’s unlikely to happen again. But if you want to be absolutely sure, some women use a double trigger shot the next time. This is when you inject not one but TWO vials of Ovidrel (the usual trigger used in NZ), one after the other. Very important: The vials should come from two different batches (check the batch numbers on the packet before signing them out and taking them home – you can’t return injectable drugs for exchange or refund). I’ve not seen any mention that this could have any adverse effect on the egg quality – it’ll cost you some $$ for one more vial of trigger (but this is cheaper than one more IVF cycle and a lot cheaper than the baby once he/she arrives!), but apart from that, it’s a “won’t hurt, might help” measure as far as I can tell. But ask your dr.

Another theory floated a lot is that you may have ovulated just before retrieval, but not so long before that they would have seen collapsed follies. The remedy for this, if true (and it’s very hard to tell) is to schedule your egg collection just a bit earlier – say, 34 to 35 hours after trigger, instead of the usual 36. Reasons to hesitate about doing this might be if several of the eggs that were retrieved were immature – collecting early could exacerbate this problem.

A rather delicate theory to probably NOT raise with your specialist is that the person doing the retrieval wasn’t very skilled. Yes, well, obviously a possibility, but hard to tell as a patient, and there’s no way you’ll get an admission about this one!! If you’ve had several cycles with ’empty’ follies, was it the same person doing the procedure each time?

OK, time to start thinking outside the very simple boxes outlined above. One possibility is that the protocol disagrees with you – gets you follies but most of them are ‘decoys’. Now, you won’t get far on this one if you are under one of NZ’s one-size-fits-all specialists. Obviously, there are some cases where a change in protocol might be risky (e.g. greater risk of overstimulation, OHSS), but personally, I couldn’t bear to go into a new cycle on the exact same protocol as a failed one, so ask lots of questions about alternatives – and see also the post: What are the main IVF protocols used in NZ? The other protocol-related thing to ask about is what stims are being used. In NZ, just about everyone gets put on straight FSH (Gonal F or Puregon), but some specialists will add some LH (e.g. Luveris) into the mix. This seems to help some women with egg quantity or quality or both; others seem to do better on straight FSH.

Some fertility specialists say that if your eggs are overcooked, i.e. if you stim too long before triggering and the egg over-ripens, then the resulting egg will stick to the follicle lining and not come out easily. The same is said about eggs that are ‘undercooked’ (i.e. if you triggered too early and the egg is not yet mature). Although there is some empirical research on the best time to trigger based on follicle size, it’s become quite clear to me (after listening to others’ experiences) that one size does not fit all, and some women need to trigger earlier than the norm, some a bit later.

The other possibility is that maybe your ovaries are of the “less is more” variety, so that if you halve your dose you may get fewer follies but the eggs in them are likely to be (a) really there and (b) better quality. I haven’t seen a lot of research on the latter, but I have talked to a low-stim specialist about this in some depth, and also to several women who swear they get far fewer empty follies when they are on a much lower dose. [And, I suppose my experience was similar numbers but better embryo quality, so I’m a fan of the low-dose option in general.] Internationally there is a fast-growing interest in the reproductive endocrinology (fertility specialists) community about low-stim and natural approaches to IVF.One of the more interesting recent innovations in IVF is in vitro maturation (IVM), where the eggs are removed from the follicles while immature and then matured in the lab. This is nil to near-nil stims technology. Last I heard – in a Nov 2007 National Radio interview with Dr. Simon Kelly (Fertility Associates Auckland) it hadn’t been approved by the ethics people, but it may be by now, or thatÂ may be coming soon. If it sounds interesting, get yourself a consultation with Simon – he did a post-doc fellowship at McGill in Montreal, where IVM was pioneered.

OK, there’s a big laundry list of possibilities here. My own experience grappling with infertility has taught me to push back quite hard if only the “we can’t do anything about it – you just have bad eggs” explanation is being offered. OK, the bad eggs thing may be true (and in my case it certainly was, since I was IVFing over 40 and with high FSH!), but that doesn’t mean there aren’t some other treatable explanations that are also in play. There are quite a few non-drastic options here to tinker with the protocol, and IMHO they are well worth discussing seriously with your dr. If he or she is reluctant, make sure you ask whether your specialist thinks this is likely to be risky or harmful in some way, or whether they think it’s relatively harmless but just unlikely to be effective. If it’s the latter, and if your instincts are telling you it makes sense, then ask to try it.

3 Responses to “We did IVF but had heaps of empty follicles – help!”

I am 43. I’ve had 6 IVF cycles between the age of 41 and 43. I got between 3 and 14 eggs retrieved in previous cycles with fertilization rates of 80-100%. Got pregnant twice but miscarried. In my last cycle, this August, scans showed 10 follicles of reasonable size. However, only 1 egg was retrieved, despite repeated flushing of the follicles.
Doctors were very surprised as I seemed to have responded well to stimulation (good estradiol rise, etc) and could not offer many explanations. They basically mentioned two possibilities for the failure to retrieve eggs:
1. an age related phenomenon and therefore now a recurrent problem

2. a one off situation related to this cycle and something they were not able to measure or see, in which case this should not be recurrent

The protocol that I followed is below, as well as other factors that could have affected this cycle.

I am left wondering whether I should try one more cycle. Also, I wonder what kind of protocol I should follow. This was a heavy-dose protocol, and the first time I took 600 U of gonadotropins. So, I’ve been looking at something different and am considering a mild stimulation protocol. Any hints, suggestions or advice?

It’s really hard to know whether your latest response was a one-off or a permanent shift.

I summarised everything I’ve learned over the years about what works for women over 40 in this post What seems to work for … women over 40 – and I think these things are even less ambiguous once we pass the age of 42.

If a little voice inside you is saying you don’t feel ‘done’ until you try just one more different strategy, then my instinct would be to go for it so you don’t look back and regret not doing so. Well, that was how I felt anyway.

As for heavy vs mild dose, I finally had success on mild after many tries at higher doses, so that’s where my thinking gravitates to naturally. But, every woman is different, and you and your dr know your body better than I do. At the same time, I do recall how it really felt like progress to finally try something different, so that may be a consideration for you.

Hi – great post.
I’m just about to start IVM shortly and am going to try and document my journey as there isn’t a lot of kiwi based sites about IVM out there yet.
Blogging at http://sweetconception.blogspot.co.nz/. I agree with your philosphy that knowledge is power and I’ve found reading about other’s experiences reallu useful so I’m hoping that others might get something out of my experiences.